Table 1.
Selected examples of shielding the OV from host barriers
| Strategy | Approach | Viral platform | Tumor type | Outcome | References |
|---|---|---|---|---|---|
| Cell-based delivery | Mesenchymal stem cell (bone marrow derived) | MV | Liver cancer | Evasion of host immunity in setting of systemic delivery | 27 |
| Mesenchymal stromal cell | Ad | Pancreatic tumor | Decreased expression of CD24 and Ki67 and enhanced activity of caspase-3 | 28 | |
| Neural stem cell | Ad | GBM | Single administration of oncolytic virus-loaded NSCs allows for up to 31% coverage of intracranial tumors | 29 | |
| Activated T-cells | VSV | Ovarian cancer | Increased efficiency compared to nonactivated T-cells | 30 | |
| Immortalized cell line from solid tumor HeLa (cervical carcinoma) A549 (lung carcinoma) MCF-7 (breast carcinoma) CT26 (colorectal carcinoma) SF268 (glioblastoma) |
VSV | Murine model metastatic tumors | Ease of manipulation and propagation in vitro, but has a tendency to arrest in the small capillary beds of the lungs and fail to recirculate in animal (mice) model | 31 | |
| Dendritic cells | MV | Breast cancer | Prevention of pleural exudate in a xenograft model | 32 | |
| Sickle cell | Reovirus VSV | Melanoma | Absorption and transfection despite presence of neutralizing antibodies | 33 | |
| Macrophages | Ad | Prostate cancer | Abolishment of tumor regrowth | 34 | |
| Myeloid-derived suppressor cells | VSV | Metastatic colon tumor | Robust immunosuppressive activity, preferential migration to tumor and decreased toxicity | 35 | |
| Monocytes | Ad | Syrian hamster models of cancer | Antitumoral effect after multiple dosing | 36 | |
| Ghost erythrocytes | VSV-G | In vitro transfection | Improved transfection efficiency | 37 | |
| Physical interface with biomaterials | Encapsulation (within biomaterial) alginate | Ad | Model for shielding the adenoviruses | Enhanced transgene expression and reduced immune response | 38 |
| Encapsulation (within biomaterial) PLGA | Ad | Model for shielding the adenoviruses | Enhanced transgene expression and reduced immune response | 38 | |
| Surface modification coating with biodegradable nanoparticles (PNLG) | Ad | Model for shielding the adenoviruses | Improved efficacy and safety | 39 | |
| Chemical modification with biomaterials | PAMAM dendrimer-coated | Ad | EGFR+ cells | Increased transduction efficiency, especially in low-to-medium CAR-expressing cancer cell lines | 40 |
| Cationic polymers* (form electrostatic interactions with anionic Ad, can also be classified as physical interface) | Ad | Model for shielding the adenoviruses | Permitted ligand attachment and manipulation of molecular weight | 25 | |
| PLL (cationic polymer*) | Ad | Model for shielding the adenoviruses | Caused Ad to bind and infect cells through a pathway other than classic CAR-mediated entry PEG-PLL-Ad had gene expression ~4× compared to naked Ad |
41 | |
| Cationic lipids* | Ad | Model for shielding the adenoviruses | Increased delivery ~80× compared to naked Ad | 42 | |
| Liposomes | Resulted in effective immune shielding | ||||
| PEGylation (covalent chemical modification) | Ad VSV |
Model for shielding the adenoviruses | Increased circulation half-life Protected from neutralization | 43 | |
| Poly-HPMA | Ad | Model for shielding the adenoviruses | Increased half-life by diminishing hepatic transgene expression | 44 | |
| Polysaccharides | Ad | Model for shielding the adenoviruses | Unable to evade neutralizing antibodies | 45 | |
| Substrate-mediated viral gene delivery | Hydrogel | Ad | Model for shielding the adenoviruses | Minimized sequestration by the mononuclear phagocytic system | 46 |
| Silk-elastin-like polymer | Ad | Model for shielding the adenoviruses | Increased viral gene expression but demonstrated some acute toxicity | 47 | |
| Chitosan | Ad | Model for shielding the adenoviruses | Infectivity was observed in cells that do not express CAR | 48 | |
| Biogels: fibrin and collagen micelle based | Ad | Model for shielding the adenoviruses | Sustained release of viral particles by fibrin | 49 | |
| Microporous scaffolds (could be considered as physical interface given that coaxial electrospinning is used to encapsulate vectors) | Ad | Model for shielding the adenoviruses | Reduced macrophage activation | 50 |
Note:
*
Cationic polymers and cationic lipids may be classified as a way to stablish physical instead of chemical interface because they are formed by electrostatic interactions with anionic adenoviruses rather than through chemical conjugation.
Abbreviations: OV, oncolytic virus; MV, measles virus; Ad, adenovirus; GBM, glioblastoma multiforme; NSCs, neural stem cells; VSV, vesicular stomatitis virus; VSV-G, vesicular stomatitis virus glycoprotein G; PLGA, poly(lactic-co-glycolic acid); PNLG, poly[2-(dibutylamino)ethylamine-L-glutamate]; PAMAM, polyamidoamine; EGFR+, epidermal growth factor receptor positive; CAR, coxsackie adenovirus receptor; PLL, poly(L-lysine); PEG, polyethylene glycol; poly-HPMA, poly-N-(2-hydroxypropyl) methacrylamide.